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Developmental Neurorehabilitation Apr 2023The aim of this systematic literature review was to assess the data regarding neuromarkers used to evaluate the impact of cardiovascular surgery on neurodevelopmental...
The aim of this systematic literature review was to assess the data regarding neuromarkers used to evaluate the impact of cardiovascular surgery on neurodevelopmental pattern of children with congenital heart defects. A systematic search was performed on PubMed and Google Scholar databases. Out of 713 publications screened, 10 studies (471 patients) met the inclusion criteria. The included studies were coded on several variables: number and heterogeneity of patients (age, congenital heart defects), exclusion of patients with conditions that predispose to neurological impairment, neuroimaging workup pre- and post-surgery, neurodevelopmental assessment, interventions (part of a different study), and follow-up period. Results were reported according to PRISMA guidelines. Findings include: neuron-specific enolase and brain-derived neurotrophic factor are not reliable neuromarkers, for protein S100B different results were reported, for activin A there is lack of evidence, and glial fibrillary acidic protein could represent a reliable neuromarker for acute brain-injury. Directions for future research are discussed.
Topics: Humans; Child; Biomarkers; Cardiac Surgical Procedures; Heart Defects, Congenital; Brain Injuries; Neuroimaging
PubMed: 36710475
DOI: 10.1080/17518423.2023.2166618 -
Associated genetic variants and potential pathogenic mechanisms of brain arteriovenous malformation.Journal of Neurointerventional Surgery Jun 2023The pathogenic mechanism of brain arteriovenous malformation (bAVM) is poorly understood. A growing body of evidence indicates that genetic factors play crucial roles in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The pathogenic mechanism of brain arteriovenous malformation (bAVM) is poorly understood. A growing body of evidence indicates that genetic factors play crucial roles in bAVM. This study examined genetic variants associated with bAVM through quantitative synthesis and qualitative description of literature.
METHODS
Five databases were searched to gather potentially relevant articles published up to January 2022. STATA 14.0 software was used for statistical analyses. Pooled odds ratios and 95% confidence intervals were calculated with random effect models, and heterogeneity was assessed using the Cochran Q test and quantified with the I test. Sensitivity and publication bias were analyzed to test the robustness of the associations. Variants identified in only one study or with great heterogeneity were not suitable for pooling association analysis, and therefore a qualitative systematic review was performed.
RESULTS
In total, 30 papers were included in a systematic review involving 4709 cases and 7832 controls, where 17 papers were in a meta-analysis. A suggested association of bAVM was observed with rs2071219 in the additive model and rs1333040 in the recessive and additive models. Other variants of genes that could not be analyzed were summarized by qualitative description. These genes were mostly involved in bone morphogenic protein/transforming growth factor beta (BMP/TGF-β), vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR), and RAS-mitogen activated protein kinase (MAPK) signaling and inflammation.
CONCLUSIONS
According to our meta-analysis, rs2071219 and rs1333040 were potentially associated with bAVM. Multiple pathological signaling pathways could affect disease development. Future studies should aim to determine the interaction of candidate genes with environmental risk factors and to elucidate detailed mechanisms of action of variants and genes.1.
Topics: Humans; Intracranial Arteriovenous Malformations; Vascular Endothelial Growth Factor A; Brain; Signal Transduction; Activin Receptors, Type II
PubMed: 35470246
DOI: 10.1136/neurintsurg-2022-018776 -
Human Reproduction Update Sep 2019Adenomyosis commonly occurs with abnormal uterine bleeding (AUB) and is associated with subfertility and a higher miscarriage rate. Recent evidence showed abnormal...
BACKGROUND
Adenomyosis commonly occurs with abnormal uterine bleeding (AUB) and is associated with subfertility and a higher miscarriage rate. Recent evidence showed abnormal vascularization in the endometrium in patients with adenomyosis, suggesting a role of angiogenesis in the pathophysiology of AUB and subfertility in adenomyosis and providing a possible treatment target.
OBJECTIVE AND RATIONALE
We hypothesized that the level of abnormal vascularization and expression of angiogenic markers is increased in the ectopic and eutopic endometrium of adenomyosis patients in comparison with the endometrium of control patients. This was investigated through a search of the literature.
SEARCH METHODS
A systematic search was performed in PubMed and Embase until February 2019. Combinations of terms for angiogenesis and adenomyosis were applied as well as AUB, subfertility or anti-angiogenic therapy. The main search was limited to clinical studies carried out on premenopausal women. Original research articles focusing on markers of angiogenesis in the endometrium of patients with adenomyosis were included. Studies in which no comparison was made to control patients or which were not published in a peer-reviewed journal were excluded. A second search was performed to explore the therapeutic potential of targeting angiogenesis in adenomyosis. This search also included preclinical studies.
OUTCOMES
A total of 20 articles out of 1669 hits met our selection criteria. The mean vascular density (MVD) was studied by quantification of CD31, CD34, von Willebrand Factor (vWF) or factor-VIII-antibody-stained microvessels in seven studies. All these studies reported a significantly increased MVD in ectopic endometrium, and out of the six articles that took it into account, four studies reported a significantly increased MVD in eutopic endometrium compared with control endometrium. Five articles showed a significantly higher vascular endothelial growth factor expression in ectopic endometrium and three articles in eutopic endometrium compared with control endometrium. The vascular and pro-angiogenic markers α-smooth muscle actin, endoglin, S100A13, vimentin, matrix metalloproteinases (MMPs), nuclear factor (NF)-kB, tissue factor (TF), DJ-1, phosphorylated mammalian target of rapamycin, activin A, folli- and myostatin, CD41, SLIT, roundabout 1 (ROBO1), cyclooxygenase-2, lysophosphatidic acid (LPA) 1,4-5, phospho signal transducer and activator of transcription 3 (pSTAT3), interleukin (IL)-6, IL-22 and transforming growth factor-β1 were increased in ectopic endometrium, and the markers S100A13, MMP-2 and -9, TF, follistatin, myostatin, ROBO1, LPA1 and 4-5, pSTAT3, IL-6 and IL-22 were increased in eutopic endometrium, compared with control endometrium. The anti-angiogenic markers E-cadherin, eukaryotic translation initiation factor 3 subunit and gene associated with retinoic-interferon-induced mortality 19 were decreased in ectopic endometrium and IL-10 in eutopic endometrium, compared with control endometrium. The staining level of vWF and two pro-angiogenic markers (NF-κB nuclear p65 and TF) correlated with AUB in patients with adenomyosis. We found no studies that investigated the possible relationship between markers of angiogenesis and subfertility in adenomyosis patients. Nine articles reported on direct or indirect targeting of angiogenesis in adenomyosis-either by testing hormonal therapy or herbal compounds in clinical studies or by testing angiogenesis inhibitors in preclinical studies. However, there are no clinical studies on the effectiveness of such therapy for adenomyosis-related AUB or subfertility.
WIDER IMPLICATIONS
The results are in agreement with our hypothesis that increased angiogenesis is present in the endometrium of patients with adenomyosis compared with the endometrium of control patients. It is likely that increased angiogenesis leads to fragile and more permeable vessels resulting in adenomyosis-related AUB and possibly subfertility. While this association has not sufficiently been studied yet, our results encourage future studies to investigate the exact role of angiogenesis in the etiology of adenomyosis and related AUB or subfertility in women with adenomyosis in order to design curative or preventive therapeutic strategies.
Topics: Adenomyosis; Adult; Angiogenesis Inhibitors; Capillary Permeability; Endometrium; Female; Humans; Infertility, Female; Neovascularization, Pathologic; Uterine Hemorrhage
PubMed: 31504506
DOI: 10.1093/humupd/dmz024 -
Menopause (New York, N.Y.) Sep 2018The associations of body mass index (BMI) and obesity with ovarian reserve are controversial. This systematic review and meta-analysis was conducted to investigate the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The associations of body mass index (BMI) and obesity with ovarian reserve are controversial. This systematic review and meta-analysis was conducted to investigate the associations in reproductive-aged women.
METHODS
PubMed and Scopus were searched up to December, 2016. Original studies on the association of BMI with ovarian reserve markers, anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), inhibin β, and antral follicle count (AFC), either according to BMI categories or a continuous variable, were selected. Analyses were stratified into three groups based on polycystic ovary syndrome (PCOS) and fertility status of women.
RESULTS
Of 4,055 records identified, 45 studies were eligible for inclusion. Comparing the obese with nonobese, the pooled mean differences (MDs) and 95% confidence intervals (CIs) were -1.08 (95% CIs -1.52, -0.63) ng/mL for AMH, -0.22 (95% CIs -0.39, -0.06) mIU/mL for FSH, -0.09 (95% CIs -0.60, 0.42) for AFC, and -21.06 (95% CIs -41.18, -0.85) pg/mL for inhibin β in overall populations. The MDs were significant for AMH in fertile non-PCOS and PCOS women, and for FSH only in PCOS women. Fisher's Z showed significant correlations of BMI with AMH in the overall populations (-0.15 [95% CIs -0.20, -0.11]) and in all subgroups, and with FSH in the fertile non-PCOS women (-0.16 [95% CIs -0.28, -0.04]).
CONCLUSION
Ovarian reserve markers of AMH and FSH are significantly lower in obese than in nonobese women, and BMI is negatively correlated with AMH in all study populations, and with FSH in fertile non-PCOS subgroups. PCOS and fertility status do not appear to affect the associations.
Topics: Adult; Anti-Mullerian Hormone; Biomarkers; Body Mass Index; Female; Fertility; Follicle Stimulating Hormone; Humans; Inhibin-beta Subunits; Linear Models; Middle Aged; Obesity; Ovarian Follicle; Ovarian Reserve; Reproduction; Statistics, Nonparametric; Young Adult
PubMed: 29738413
DOI: 10.1097/GME.0000000000001116 -
Human Reproduction Update Jan 2018Hyperglycemia can result from a loss of pancreatic beta-cells or a decline in their function leading to decreased insulin secretion or may arise from insulin resistance... (Review)
Review
BACKGROUND
Hyperglycemia can result from a loss of pancreatic beta-cells or a decline in their function leading to decreased insulin secretion or may arise from insulin resistance and variable degrees of inadequate insulin secretion resulting in diabetes and related comorbidities. To date several reviews have addressed the issue of diabetes-related male infertility but most have focused on how metabolic syndrome causes the decline in male fertility. However, a comprehensive overview as to how diabetes-induced hyperglycemia impairs male fertility is missing. Impaired regulation of glucose and the resultant hyperglycemia are major threats to the health of individuals in modern societies especially given the rapidly rising prevalence affecting an increasing number of men in their reproductive years. Consequently, diabetes-induced hyperglycemia is likely to contribute to a decline in global birth rates especially in those societies with a high diabetic prevalence.
OBJECTIVE AND RATIONALE
This systematic review addresses and summarizes the impact of hyperglycemia on male reproductive health with a particular emphasis on the molecular mechanisms that influence the testis and other parts of the male reproductive tract.
SEARCH METHODS
A systematic search of the literature published in the MEDLINE-Pubmed database (http://www.ncbi.nlm.nih.gov/pubmed) and Cochrane Library (http://www.cochranelibrary.com) was performed, as well as hand searching reference lists, from the earliest available online indexing year until May 2017, using diabetes- and male fertility-related keywords in combination with other search phrases relevant to the topic of hyperglycemia. Inclusion criteria were: clinical studies on type 1 diabetic (T1D) men and studies on T1D animal models with a focus on reproductive parameters. Case reports/series, observational studies and clinical trials were included. Studies on patients with type 2 diabetes (T2D) or animal models of T2D were excluded to distinguish hyperglycemia from other metabolic effects.
OUTCOMES
A total of 890 articles were identified of which 197 (32 clinical, 165 animal studies) were selected for qualitative analysis. While the clinical data from men with hyperglycemia-induced reproductive dysfunction were reported in most studies on T1D, the study designs were variable and lacked complete information on patients. Moreover, only a few studies (and mostly animal studies) addressed the underlying mechanisms of how hyperglycemia induces infertility. Potential causes included impaired function of the hypothalamic-pituitary-gonadal axis, increased DNA damage, perturbations in the system of advanced glycation endproducts and their receptor, oxidative stress, increased endoplasmatic reticulum stress, modulation of cellular pathways, impaired mitochondrial function and disrupted sympathetic innervation. However, intervention studies to identify and confirm the pathological mechanisms were missing: data that are essential in understanding these interactions.
WIDER IMPLICATIONS
While the effects of regulating the hyperglycemia by the use of insulin and other modulators of glucose metabolism have been reported, more clinical trials providing high quality evidence and specifically addressing the beneficial effects on male reproduction are required. We conclude that interventions using insulin to restore normoglycemia should be a feasible approach to assess the proposed underlying mechanisms of infertility.
Topics: Animals; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Infertility, Male; Insulin; Male; Mitochondrial Diseases; Reproduction
PubMed: 29136166
DOI: 10.1093/humupd/dmx033 -
Annals of Medicine 2015Our objective was to perform a meta-analysis examining the sensitivity of pulsatility index (PI) and various biomarkers and PI and mean arterial pressure (MAP) for the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Our objective was to perform a meta-analysis examining the sensitivity of pulsatility index (PI) and various biomarkers and PI and mean arterial pressure (MAP) for the prediction of pre-eclampsia.
MATERIAL AND METHODS
PubMed, CENTRAL, and Embase databases were searched from inception until 8 May 2014 using combinations of the search terms: pre-eclampsia, ultrasonography, pregnancy, biomarker, mean arterial pressure, placental protein 13, pregnancy-associated plasma protein-A, placental growth factor, activin A, inhibin A, pulsatility index. The pooled sensitivity of PI + biomarkers and PI + MAP were calculated, and reported with corresponding 95% confidence intervals (CIs).
RESULTS
Fifteen studies were included in the meta-analysis. The pooled sensitivity of all biomarkers for the prediction of pre-eclampsia was 0.669 (95% CI 0.610-0.723), for the prediction of early-onset pre-eclampsia was 0.830 (95% CI 0.794-0.861), and for the prediction of late-onset pre-eclampsia was 0.564 (95% CI 0.499-0.627). Similarly, the predictive ability of PI + MAP for early-onset pre-eclampsia was good (sensitivity 0.894), while that for late-onset was poor (sensitivity 0.570).
CONCLUSION
The combination of PI and different biomarkers or MAP exhibits a good predictive ability for early-onset pre-eclampsia, and poor predictive ability for late-onset pre-eclampsia.
Topics: Activins; Biomarkers; Blood Pressure; Female; Galectins; Humans; Inhibins; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Pregnancy Proteins; Pregnancy-Associated Plasma Protein-A; Pulsatile Flow; Sensitivity and Specificity
PubMed: 26153822
DOI: 10.3109/07853890.2015.1059483 -
Obstetrical & Gynecological Survey Apr 2011Preeclampsia (PE) affects 1% to 2% of pregnant women and is a leading cause of maternal and perinatal morbidity and mortality worldwide. The clinical syndrome of PE... (Review)
Review
UNLABELLED
Preeclampsia (PE) affects 1% to 2% of pregnant women and is a leading cause of maternal and perinatal morbidity and mortality worldwide. The clinical syndrome of PE arises in the second half of pregnancy. However, many underlying factors including defective placentation may already be apparent in the first and early second trimester in many patients. In clinical practice, there is currently no reliable screening method in the first trimester of pregnancy with sufficient accuracy to identify women at high risk to develop PE. Early identification of high-risk pregnancy may facilitate the development of new strategies for antenatal surveillance or prevention and thus improve maternal and perinatal outcome. The aim of this systematic review was to study the literature on the predictive potential of first-trimester serum markers and of uterine artery Doppler velocity waveform assessment (Ut-A Doppler). Literature on the 7 most studied serum markers (ADAM12, fβ-hCG, Inhibin A, Activin A, PP13, PlGF, and PAPP-A) and Ut-A Doppler was primarily selected. In the selected literature, a combination of these markers was analyzed, and where relevant, the value of maternal characteristics was added. Measurements of serum markers and Ut-A Doppler were performed between week 8 + 0 and 14 + 0 GA. Low levels of PP13, PlGF, and PAPP-A and elevated level of Inhibin A have been found to be significantly associated with the development of PE later in pregnancy. The detection rates of single markers, fixed at 10% false-positive rate, in the prediction of early-onset PE were relatively low, and ranged from 22% to 83%. Detection rates for combinations of multiple markers varied between 38% and 100%. Therefore, a combination of multiple markers yields high detection rates and is promising to identify patients at high risk of developing PE. However, large scale prospective studies are required to evaluate the power of this integrated approach in clinical practice.
TARGET AUDIENCE
Obstetricians and Gynecologists, Family physicians Learning Objectives: After completion of this article, the reader should be better able to appraise the recent literature on the development of preeclampsia in the first-trimester, evaluate the predictive value of first-trimester markers and use first-trimester markers, either individually or in combination, to assess the risk of preeclampsia.
Topics: Biomarkers; Female; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Ultrasonography, Doppler; Uterine Artery
PubMed: 21756405
DOI: 10.1097/OGX.0b013e3182227027 -
Annales de Biologie Clinique 2011Using a series of keywords, we reviewed electronic databases (Medline, Embase, all records to May 2009) reporting the performance of biological and ultrasonographic... (Review)
Review
Using a series of keywords, we reviewed electronic databases (Medline, Embase, all records to May 2009) reporting the performance of biological and ultrasonographic markers to predict preeclampsia, both single markers and combinations of markers. We analyzed the data according to gestational age and risk levels of the studied populations. We evaluated the methodological quality of included publications using QUADAS (quality assessment of diagnostic accuracy studies). We identified 37 relevant studies that assessed 71 different combinations of biochemical and ultrasonographic markers. Most studies were performed during the second trimester on small-scale high-risk populations with few cases of preeclampsia. Combinations of markers generally led to an increase in sensitivity and/or specificity compared with single markers. In low-risk populations, combinations including placental protein 13 (PP13), pregnancy-associated plasma protein A (PAPP-A), a disintegrin and metalloprotease-12 (ADAM12), activin A, or inhibin Ameasured in first or early second trimester and uterine artery Doppler in second trimester appear promising (sensitivity 60%-80%, specificity > 80%). In high-risk populations, the combination of PP13 and pulsatility index in first trimester showed 90% sensitivity and 90% specificity in a single study limited to severe preeclampsia. Combinations of biochemical and ultrasonographic markers improved the performance of early prediction of preeclampsia. From a perspective of integrative medicine, large population-based studies evaluating algorithms combining multiple markers are needed, if screening approaches are to be eventually implemented.
Topics: Biomarkers; Female; Humans; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Ultrasonography
PubMed: 21659041
DOI: 10.1684/abc.2011.0572 -
Clinical Chemistry Mar 2010Early identification of pregnant women at risk for preeclampsia is a priority to implement preventive measures. Some biochemical and ultrasonographic parameters have... (Review)
Review
BACKGROUND
Early identification of pregnant women at risk for preeclampsia is a priority to implement preventive measures. Some biochemical and ultrasonographic parameters have shown promising predictive performance, but so far there is no clinically validated screening procedure.
CONTENT
Using a series of keywords, we reviewed electronic databases (Medline, Embase, all records to May 2009) reporting the performance of biological and ultrasonographic markers to predict preeclampsia, both single markers and combinations of markers. We analyzed the data according to gestational age and risk levels of the studied populations. We evaluated the methodological quality of included publications using QUADAS (quality assessment of diagnostic accuracy studies). We identified 37 relevant studies that assessed 71 different combinations of biochemical and ultrasonographic markers. Most studies were performed during the second trimester on small-scale high-risk populations with few cases of preeclampsia. Combinations of markers generally led to an increase in sensitivity and/or specificity compared with single markers. In low-risk populations, combinations including placental protein 13 (PP13), pregnancy-associated plasma protein A (PAPP-A), a disintegrin and metalloprotease-12 (ADAM12), activin A, or inhibin A measured in first or early second trimester and uterine artery Doppler in second trimester appear promising (sensitivity 60%-80%, specificity >80%). In high-risk populations, the combination of PP13 and pulsatility index in first trimester showed 90% sensitivity and 90% specificity in a single study limited to severe preeclampsia.
SUMMARY
Combinations of biochemical and ultrasonographic markers improved the performance of early prediction of preeclampsia. From a perspective of integrative medicine, large population-based studies evaluating algorithms combining multiple markers are needed, if screening approaches are to be eventually implemented.
Topics: Biochemistry; Biomarkers; Female; Humans; Pre-Eclampsia; Pregnancy; Ultrasonography, Prenatal
PubMed: 20044446
DOI: 10.1373/clinchem.2009.134080 -
Human Reproduction Update 2010It has been suggested that body mass index (BMI), especially obesity, is associated with subfertility in men. Semen parameters are central to male fertility and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It has been suggested that body mass index (BMI), especially obesity, is associated with subfertility in men. Semen parameters are central to male fertility and reproductive hormones also play a role in spermatogenesis. This review aimed to investigate the association of BMI with semen parameters and reproductive hormones in men of reproductive age.
METHODS
MEDLINE, EMBASE, Biological Abstracts, PsycINFO and CINAHL databases and references from relevant articles were searched in January and February 2009. Outcomes included for semen parameters were sperm concentration, total sperm count, semen volume, motility and morphology. Reproductive hormones included were testosterone, free testosterone, estradiol, FSH, LH, inhibin B and sex hormone binding globulin (SHBG). A meta-analysis was conducted to investigate sperm concentration and total sperm count.
RESULTS
In total, 31 studies were included. Five studies were suitable for pooling and the meta-analysis found no evidence for a relationship between BMI and sperm concentration or total sperm count. Overall review of all studies similarly revealed little evidence for a relationship with semen parameters and increased BMI. There was strong evidence of a negative relationship for testosterone, SHBG and free testosterone with increased BMI.
CONCLUSIONS
This systematic review with meta-analysis has not found evidence of an association between increased BMI and semen parameters. The main limitation of this review is that data from most studies could not be aggregated for meta-analysis. Population-based studies with larger sample sizes and longitudinal studies are required.
Topics: Adolescent; Adult; Body Mass Index; Gonadal Hormones; Humans; Infertility, Male; Inhibin-beta Subunits; Male; Middle Aged; Obesity; Semen; Semen Analysis; Sex Hormone-Binding Globulin; Testosterone; Young Adult
PubMed: 19889752
DOI: 10.1093/humupd/dmp047